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Oral Enrichment of Streptococcus and its Role in Systemic Inflammation Related to Monocyte Activation in Humans with Cocaine Use Disorder

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Abstract

Cocaine use is commonly associated with increased chronic systemic inflammation. However, the drivers for cocaine use-mediated systemic inflammation are not fully understood. In the current study, we recruited individuals with cocaine use disorder and healthy individuals who did not use cocaine and collected paired saliva and blood samples. The saliva samples were used to assess the oral microbiome, and the plasma samples were evaluated for 33 cytokines and chemokines. Cocaine users exhibited decreased saliva microbial diversities compared to non-users. Streptococcus was the only increased genus in the saliva from cocaine users, whereas several genera were decreased in cocaine users compared to non-users. Notably, cocaine users exhibited increased plasma levels of several monocyte activation markers, including monocyte chemoattractant protein (MCP)-4, macrophage inflammatory protein (MIP)-3α, macrophage-derived chemokine (MDC), and thymus and activation-regulated chemokine (TARC), all of which were correlated with increased saliva levels of three Streptococcus species. Furthermore, treatment with Streptococcus or its lipoteichoic acid preferentially activated primary human monocytes to produce proinflammatory cytokines and chemokines, such as MIP-3α and TARC, in vitro compared to controls. However, monocytes failed to produce these chemokines after exposure to cocaine or cocaine plus bacteria compared to medium or bacteria alone. This study revealed that chronic cocaine use-associated inflammation in the blood may result from increased oral Streptococcus and its effects on myeloid cell activation, but does not result from cocaine directly.

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Acknowledgements

This work was supported by grants from the National Institute of Drug Abuse K24DA038240 (McRae-Clark), R01 DA045596 (Fitting), NR016928 (Cong), ONF RE01 and P20NR016605 (Starkweather)—Pilot 3 sub-award (Xu), and R01DA043938 (Stoops).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Ave. BSB208D, Charleston, SC, 29425, USA

    Xiaoyu Fu, Da Cheng, Zhenwu Luo, Zhuang Wan & Wei Jiang

  2. Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, 410008, China

    Xiaoyu Fu & Da Cheng

  3. Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA

    Amanda Wagner & Aimee McRae-Clark

  4. Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, NC, 27599, Chapel Hill, USA

    Sylvia Fitting

  5. School of Nursing, Institute for Systems Genomics, Department of Pediatrics, School of Medicine, University of Connecticut, Storrs, CT, USA

    Xiaomei Cong

  6. Microbial Analysis, Resources, and Services, University of Connecticut, Storrs, CT, USA

    Wanli Xu & Kendra Maas

  7. Department of Pathology, Ohio State University College of Medicine, Columbus, OH, USA

    Jian Zhu

  8. Hunan Normal University College of Life Sciences, Changsha, China

    Zejun Zhou

  9. Department of Behavioral Science, Department of Psychiatry, Center On Drug and Alcohol Research, Unviersity of Kentucky College of Medicine and College of Arts and Sciences, Lexington, KY, 40536, USA

    William W. Stoops

  10. Ralph H. Johnson VA Medical Center, Charleston, 29403, USA

    Aimee McRae-Clark

  11. Divison of Infectious Diseases, Department of Medicine, Medical University of South, 173 Ashley Ave. BSB208D, Charleston, SC, 29425, USA

    Wei Jiang

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  1. Xiaoyu Fu
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  2. Da Cheng
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Contributions

X.F, D.C, Z.Z, and L.Z performed experiments. X.F wrote the manuscript. Z.W, L.Z, W.X, and W.J analysed data. K.M conducted microbial sequencing. A.W., and A.M. recruited participants, identified cocaine use disorder, and conceived the study. S.F., X.C., J. Z., W. S., and W. J., conceived the study and revised the manuscript.

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Correspondence to Wei Jiang.

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The authors declare no competing interests. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Fu, X., Cheng, D., Luo, Z. et al. Oral Enrichment of Streptococcus and its Role in Systemic Inflammation Related to Monocyte Activation in Humans with Cocaine Use Disorder. J Neuroimmune Pharmacol 17, 305–317 (2022). https://doi.org/10.1007/s11481-021-10007-6

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